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Updated: Dec 20, 2025
Modeling Brain Metastases Through Intracranial Injection and Magnetic Resonance Imaging
Published on: June 7, 2020
Cellular and Molecular Changes of Brain Metastases-Associated Myeloid Cells during Disease Progression and
Michael Schulz1, Birgitta Michels2, Katja Niesel3
1Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany; Biological Sciences, Faculty 15, Goethe University Frankfurt, Frankfurt am Main, Germany.
Abstract:
Brain-resident microglia and bone marrow-derived macrophages represent the most abundant non-cancerous cells in the brain tumor microenvironment with critical functions in disease progression and therapeutic response. To date little is known about genetic programs that drive disease-associated phenotypes of microglia and macrophages in brain metastases. Here we used cytometric and transcriptomic analyses to define cellular and molecular changes of the myeloid compartment at distinct stages of brain metastasis and in response to radiotherapy. We demonstrate that genetic programming of tumor education in myeloid cells occurs early during metastatic onset and remains stable throughout tumor progression. Bulk and single cell RNA sequencing revealed distinct gene signatures in brain-resident microglia and blood-borne monocytes/macrophages during brain metastasis and in response to therapeutic intervention. Our data provide a framework for understanding the functional heterogeneity of brain metastasis-associated myeloid cells based on their origin.
Insights
Genetic programming of myeloid cells in brain metastases begins early and persists. Microglia and macrophages show distinct gene signatures, offering insights into their roles in brain tumor progression and treatment response.
Area of Science:
- Neuro-oncology
- Immunology
- Genomics
Background:
- Microglia and macrophages are key non-cancerous cells in the brain tumor microenvironment.
- Their roles in brain metastasis progression and treatment response are not fully understood.
- Little is known about the genetic drivers of their disease-associated phenotypes.
Purpose of the Study:
- To define cellular and molecular changes in myeloid cells during brain metastasis.
- To investigate the impact of radiotherapy on these myeloid cells.
- To understand the genetic programs shaping microglia and macrophages in brain metastases.
Main Methods:
- Cytometric and transcriptomic analyses were employed.
- Bulk and single-cell RNA sequencing were utilized.
- Studies were conducted at distinct stages of brain metastasis and post-radiotherapy.
Main Results:
- Myeloid cell 'tumor education' occurs early and is stable throughout metastasis progression.
- Distinct gene signatures were identified in brain-resident microglia versus blood-borne monocytes/macrophages.
- These signatures differ during metastasis and in response to therapeutic intervention.
Conclusions:
- Myeloid cell programming in brain metastases is an early and stable process.
- Origin dictates the functional heterogeneity of myeloid cells in brain metastases.
- Provides a framework for understanding myeloid cell roles in brain tumors.
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